EARLY TREATMENT OF STROKE WITH MONOSIALOGANGLIOSIDE GM-1 - EFFICACY AND SAFETY RESULTS OF THE EARLY STROKE TRIAL

Background and Purpose The Early Stroke Trial (EST) is a randomized, d ouble-blind, placebo-controlled trial to assess the effect of monosial oganglioside GM-1 in improving recovery in patients who experienced an ischemic supratentorial stroke. Methods Sixteen clinical centers recr uited 805 patients, of whom 792 were confirmed to be eligible. Treatme nt, consisting of a first dose of either 200 mg GM-1 or placebo, was i nitiated within 5 hours of the onset of stroke; a second dose of eithe r 100 mg GM-1 or placebo was administered 12 hours later. Thereafter, patients received a daily injection of 100 mg GM-1 or placebo intraven ously from day 2 through 10 and intramuscularly from day 11 through 21 . Patients were followed up for a total of 4 months. Results Survival was similar in the two treatment groups. Improvement in neurological s tatus, as measured by the change in Canadian Neurological Scale score between baseline and 4-month assessments, was greater in the group rec eiving GM-1; the observed difference between treatment groups was 0.22 (P=.06). A post hoc analysis in the subgroup of patients treated with in 4 hours showed a statistically significant difference, with Canadia n Neurological Scale mean improvement of 0.41 (P=.016). GM-1 use was n ot associated with differences in frequency, nature, or severity of ad verse experiences. Conclusions These findings suggest that GM-1 is saf e in the dose and treatment schedule used and that its efficacy in isc hemic stroke is greater when given soon after onset of stroke.